The candidate for this Clinical Science Research and Development Career Development Award (CDA2) is Bharati Prasad, MD, MS, a pulmonary, critical care, and sleep medicine staff physician at Jesse Brown VAMC. Dr. Prasad's academic appointment is as a tenure-track Assistant Professor at the University of Illinois at Chicago (UIC). Dr. Prasad's long-term career goals are to become an independent physician-scientist developing effective strategies to reduce cardiovascular disease (CVD) in diverse populations through interventions that optimize sleep and breathing. To achieve her goals, Dr. Prasad has assembled a comprehensive career development plan and a strong team of mentors with longstanding VA and other federal funding and mentorship experience. Her primary mentor, Frances M. Weaver PhD, is a VA Research Career Scientist and an experienced clinical trialist. Her co- mentors are David W. Carley, PhD (an expert in autonomic derangements associated with Obstructive Sleep Apnea; OSA and developing novel treatment interventions for OSA) and Samuel T. Kuna, MD, with expertise in Continuous Positive Airway Pressure (CPAP) treatment intervention trials in patients with OSA and an extensive research record in the VA. The proposal also includes a multidisciplinary team of collaborators with expertise in the areas of measurement of biomarkers key to the pathogenesis of hypertension in OSA, genetic ancestry in biomedical research, early non-invasive assessment of vascular dysfunction, and longitudinal data analyses. The proposal leverages the extensive research and clinical resources at Jesse Brown VAMC, including a large pool of diverse Veteran populations served. Obstructive Sleep Apnea (OSA) and hypertension are both common and severe problems in African American individuals (as noted in the International Society on Hypertension in Blacks consensus statement). CPAP treatment of OSA is effective in controlling hypertension in patients with OSA, but has not been studied in African Americans, a high-risk population with potentially large health gains. This is an area of significance because poorly controlled hypertension leads to progression of CVD and morbidity in this population. By identifying CPAP treatment-response and relevant moderators of this response in African Americans with hypertension and OSA, targeted treatment of OSA can be implemented, reducing the excess burden of CVD. We will determine the relative magnitude of hypertension response to CPAP treatment (ambulatory blood pressure and central aortic blood pressure) in 220 African American and European American Veterans with hypertension and newly diagnosed OSA (specific aim 1). We will measure changes in pathogenic biomarkers (urinary cumulative sympathetic nervous system activity and oxidative stress) that are responsive to CPAP treatment in addition to hypertension assessments. Further, we will examine the role of excessive daytime sleepiness (EDS), a potentially important moderator of treatment response, in these two patient populations (specific aim 2). Finally, we will adjust our outcomes assessment for the anticipated biological heterogeneity among self-identified African Americans by measuring genetic ancestry (exploratory aim). This award will provide the foundation for the goals of this research program to reduce CVD disparity in diverse populations with targeted treatment of OSA.